1.Increased Serum High Mobility Group Box 1 (HMGB1) Concentration and the Altered Expression of HMGB1 and Its Receptor Advanced Glycation Endproducts in Pemphigus.
Jia Yi LI ; Yong Hong LU ; Li Wen ZHANG ; Pei Mei ZHOU ; Tao CHEN
Annals of Dermatology 2017;29(1):121-123
No abstract available.
HMGB1 Protein*
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Pemphigus*
2.High mobility group box 1 levels as potential predictors of asthma severity.
Shuanglan XU ; Weihua LIU ; Liuchao ZHANG ; Quan HE ; Chenhui MA ; Jingxian JIANG ; Sheng YE ; Linyang GE ; Zi CHEN ; Linfu ZHOU
Chinese Medical Journal 2023;136(13):1606-1608
3.HMGB1-a as potential target for therapy of hematological malignancies.
Ya-Hui HU ; Lu YANG ; Chen-Guang ZHANG
Journal of Experimental Hematology 2014;22(2):560-564
HMGB1 is a widely existing DNA-binding nuclear protein, participating in gene transcription, damage repair, recombination and stabilizing nucleosome construction. Under injury, infection and chemotherapy, HMGB1 can be released by nature immunocyte and necrosis cells as a DAMP, exerting pleiotropic biological effects by binding to RAGE, TLR and CXCL12, which lead to activation of CDC42, mitogen-activated protein kinases (MAPKs), c-IAP and NF-κB, thereby promoting angiogenesis, unlimited replicative potential, tissue invasion and metastasis. And it also involves in immune response by regulating immunocyte function as a immunocyte warning signal. Scholars have detected that HMGB1 is over expressed and released following chemotherapy and radiation therapy in cells of hematological malignancies, promoting malignant cell replication, decreasing therapeutic effect. Recently, endogenous HMGB1 has been implied to be an intrinsic modulator of autophagy and referenced to resistant to apoptosis in malignant hematosis cells. In contrast, through suppression of HMGB1 expression, tumor cell apoptosis and chemotherapeutic drug sensitivity were increased, which will be a new strategy for the treatment of hematological malignancies. In this article, the basic characteristics of HMGB1, including structure and biological features, and HMGB1 and tumors such as lymphoma, myeloproliferative neoplasms and acute myeloid leukemia are reviewed.
Animals
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HMGB1 Protein
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Hematologic Neoplasms
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therapy
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Humans
5.Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism.
Ying-Yi LUAN ; Feng-Hua YAO ; Qing-Hong ZHANG ; Xiao-Mei ZHU ; Ning DONG ; Yong-Ming YAO
Chinese Journal of Applied Physiology 2012;28(6):548-554
High mobility group box-1 protein (HMGB1), which is a nuclear protein, participates in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury. In the initial stage of injury, there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens, but this pro-inflammatory period is transient, and it is followed by a prolonged period of immune suppression. At present, several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity, which may enhance the production of early proinflammatory mediators, and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity. The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation, however, this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.
Cytokines
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immunology
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HMGB1 Protein
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immunology
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Humans
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Immunity, Cellular
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Inflammation
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immunology
6.Eosinophils Modulate CD4+ T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma.
Eun Jin SHIM ; Eunyoung CHUN ; Hyun Seung LEE ; Bo Ram BANG ; Sang Heon CHO ; Kyung Up MIN ; Heung Woo PARK
Allergy, Asthma & Immunology Research 2015;7(2):190-194
Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of asthma. The supernatant of the eosinophil culture was found to significantly increase the levels of interleukin (IL)-4 and IL-5 in the supernatant of CD4+ T cells co-cultured with DCs. HMGB1 levels increased in the supernatant of the eosinophil culture stimulated with IL-5. Anti-HMGB1 antibodies significantly attenuated increases of IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with DCs that were induced by the supernatant of the eosinophil culture. In addition, anti-HMGB1 antibodies significantly attenuated the expressions of activation markers (CD44 and CD69) on CD4+ T cells. Our data suggest that eosinophils modulate CD4+ T cell responses via HMGB1 in the pathogenesis of asthma.
Antibodies
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Asthma*
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Dendritic Cells
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Eosinophils*
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HMGB1 Protein
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Inflammation
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Interleukin-4
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Interleukin-5
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Interleukins
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T-Lymphocytes
7.HMGB1-Binding Heptamer Confers Anti-Inflammatory Effects in Primary Microglia Culture.
Experimental Neurobiology 2013;22(4):301-307
High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the postischemic brain, HMGB1 is massively released during NMDA-induced acute damage and triggers inflammatory processes. In a previous study, we demonstrated that intranasally delivered HMGB1 binding heptamer peptide (HBHP; HMSKPVQ) affords robust neuroprotective effects in the ischemic brain after middle cerebral artery occlusion (MCAO, 60 minutes). In the present study, we investigated HBHP-induced anti-inflammatory effects on microglia activation. In LPS-treated primary microglia culture, HMGB1 was rapidly released and accumulated in culture media. Furthermore, LPS-conditioned media collected from primary microglia cultures (LCM) activated naive microglia and markedly induced NO and proinflammatory cytokines. However, the suppression of HMGB1 by siRNA-HMGB1, HMGB1 A box, or anti-HMGB1 antibody significantly attenuated LCM-induced microglial activation, suggesting that HMGB1 plays a critical role in this process. A pull-down assay using biotin-labeled HBHP showed that HBHP binds directly to HMGB1 (more specifically to HMGB1 A box) in LCM. In addition, HBHP consistently inhibited LCM-induced microglial activation and suppressed the inductions of iNOS and proinflammatory cytokines. Together these results suggest that HBHP confers anti-inflammatory effects in activated microglia cultures by forming a complex with HMGB1.
Brain
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Culture Media
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Cytokines
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HMGB1 Protein
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Infarction, Middle Cerebral Artery
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Inflammation
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Microglia*
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Neuroprotective Agents
8.Expression of high mobility group box-1 in colorectal cancer and its clinical significance.
Zengjun LI ; Haipeng WANG ; Bao SONG ; Yanlai SUN ; Jianjun HAN ; Zhongfa XU
Chinese Journal of Gastrointestinal Surgery 2015;18(6):616-619
OBJECTIVETo investigate the expression level of high mobility group box-1 (HMGB1) in human colorectal cancer and its relation with different clinicopathological characteristics and prognosis of colorectal cancer patients.
METHODSImmunohistochemical method was used to detect the HMGB1 expression in tissue samples of 86 colorectal cancer patients and 32 normal colorectal tissue samples. Positive rates of HMGB1 expression were compared among different clinicopathological characteristics. Relation of HMGB1 expression with survival was analyzed.
RESULTSHMGB1 expression was mainly in colorectal cancer cell nucleus, with a few appearance of co-expression in nucleus and cytoplasm. Positive rate of HMGB1 expression in normal tissues was significantly lower than that in colorectal cancers [9.4% (3/32) vs. 66.3% (57/86), P=0.000], and it was much higher in large cancers, lower differentiation, invasion to outside serosa, advanced clinical stage and lymph node metastasis (all P<0.05), but was similar in terms of age and gender (P>0.05). Survival analysis showed that 3-year survival rate of patients with positive HMGB1 expression was significantly lower as compared to those with negative HMGB1 expression (56.1% vs. 85.7%, P=0.021), meanwhile it was significantly lower in patients with co-expression in nucleus and cytoplasm as compared to those with simple nuclear expression (41.4% vs. 75.0%, P=0.013).
CONCLUSIONSHMGB1 expression in colorectal cancer is high, and its positive rate increases with the low differentiation, invasion and metastasis. HMGB1 co-expression in nucleus and cytoplasm indicates poor prognosis of colorectal cancer patients.
Cell Nucleus ; Colorectal Neoplasms ; HMGB1 Protein ; Humans ; Lymphatic Metastasis ; Prognosis ; Survival Analysis ; Survival Rate
9.Diagnostic value of high mobility group box 1 for acute appendicitis in children.
Jian-Fen HU ; Jiang-Yan WU ; Lin ZHANG ; Long-Gui YANG ; Cai-Xia LONG
Chinese Journal of Contemporary Pediatrics 2014;16(9):919-921
OBJECTIVETo evaluate the value of high mobility group box 1(HMGB1) in the diagnosis of pediatric acute appendicitis.
METHODSThe children with acute abdomen who had a diagnosis of suspected acute appendicitis between January and July 2013 and 25 healthy children were enrolled in this study. Serum HMGB1 levels were measured using ELISA on admission. The patients were classified into 2 groups according to surgery confirmation or pathological results: appendicitis (n=28) and non-appendicitis (n=35).
RESULTSSerum HMGB1 levels and WBC in the appendicitis and non-appendicitis groups were significantly higher than in the healthy children group (P<0.01). The appendicitis group showed more increased serum HMGB1 levels compared with the non-appendicitis group (median: 32.9 ng/mL vs 22.0 ng/mL; P<0.01). For a diagnosis of acute appendicitis, the sensitivity and specificity of serum HMGB1 was 71.4% and 82.9% respectively at the best cutoff of 28.0 ng/mL, with the accuracy of 77.8% and the area under the curve of 0.765 (95%CI 0.638-0.893).
CONCLUSIONSHMGB1 may play a role in the diagnosis of pediatric acute appendicitis.
Acute Disease ; Appendicitis ; blood ; diagnosis ; Child, Preschool ; Female ; HMGB1 Protein ; blood ; Humans ; Infant ; Male
10.Changes in plasma high mobility group box-1 protein levels and its relationship with sepsis in severely burned patients.
Ning DONG ; Yong-ming YAO ; Yan YU ; Chun-yu GU ; Shu-hong LEI ; Zhi-yong SHENG
Acta Academiae Medicinae Sinicae 2007;29(4):466-470
OBJECTIVETo investigate the significance of changes in plasma high mobility group box-1 protein (HMGB1) levels and its relationship with sepsis and endotojemia in severely burned patients.
METHODSTotally 25 large area burned patients ( > 30% total body surface area) were included in this study, and 8 healthy volunteers served as normal controls. The plasma levels of HMGB1 were measured by ELISA, and endotoxin concentrations was determined by the modified chromogenic limulus amebocyte lysate (LAL) assay on posthurn days 1, 3, 5, 7, 14, 21, and 28.
RESULTSThe plasma HMGBL levels were markedly elevated on postburn day 1 in severely burned patients, and they were significantly higher in septic patients than those without sepsis on days 7, 21, and 28 after burns (P<0.05). Among septic patients, plasma HMGBI levels in the survival group were significantly lower than those with fatal outcome on days 3 and 21 (P<0.05, P<0.01). No significant correlations were found between HMGB1 levels and the sizes of total body surface area (P>0.05). In addition, the plasma HMGB1 levels were positively correlated with endotoxin concentrations on days 3, 5, 7, 21 after major burns (P<0.05, P<0.01).
CONCLUSIONSHMGB1, as an important late mediators of inflammation, may be involved in the development of sepsis following extensive burns, and it can be markedly induced by endotoxemia secondary to acute insults. Dynamic measurements of circulating HMGB1 levels should be helpful to monitor the disease course and judge the prognosis of burned patients.
Burns ; blood ; microbiology ; Endotoxins ; blood ; HMGB1 Protein ; blood ; Humans ; Sepsis ; blood